| 1. |
- Ahmad, Irma, et al.
(författare)
-
High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
- 2023
-
Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.METHODS: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression.RESULTS: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+.CONCLUSION: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.
|
|
| 2. |
- Dahlgren, Markus, et al.
(författare)
-
Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
-
Tidskriftsartikel (refereegranskat)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
|
|
| 3. |
- Kauppi, Anna M., 1971-, et al.
(författare)
-
Inhibitors of type III secretion in Yersinia : design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
- 2007
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd. - 0968-0896 .- 1464-3391. ; 15:22, s. 6994-7011
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal.
|
|
| 4. |
- Nyberg, Lars, 1966-, et al.
(författare)
-
Biological and environmental predictors of heterogeneity in neurocognitive ageing : Evidence from Betula and other longitudinal studies
- 2020
-
Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 64
-
Forskningsöversikt (refereegranskat)abstract
- Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.
|
|
| 5. |
- Carlsson, Ninni, 1962, et al.
(författare)
-
”Visa i handling vad arbetet mot mäns våld är värt”
- 2019
-
Ingår i: Svenska Dagbladet. ; 2019:4 april
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Mitt i debatten om Josefin Nilsson och det våld mot henne som närstående berättar om i SVT-dokumentären ”Älska mig för den jag är”, tillkännager regeringen, C och L att de föreslår 45 miljoner i vårbudget för att bekämpa mäns våld mot kvinnor. Flera medier kallar det en storsatsning men är det verkligen det, frågar våldsforskare, #metoo-upprop och organisationer. Med hjälp av aktuell forskning argumenterar de för att detta är långt ifrån tillräckligt, kräver större vårbudget mot mäns våld mot kvinnor och bjuder in riksdag och regering till dialog.
|
|
| 6. |
|
|
| 7. |
- Johanna, Bragge, et al.
(författare)
-
Unveiling the intellectual structure and evolution of external resource management research: Insights from a bibliometric study
- 2019
-
Ingår i: Journal of Business Research. - : Elsevier BV. - 0148-2963. ; 97, s. 141-159
-
Tidskriftsartikel (refereegranskat)abstract
- In the current hyper-competitive economy, it is increasingly important to understand how firms can and should access and leverage external resources, such as customer knowledge or supply-chain partners’ capabilities. In this paper, we report the results of bibliometric analyses on external resource management (ERM) research in nine representative journals, and elaborate the underlying patterns and dynamics in this relatively young research area. A total of 1290 articles ranging from year 2000 to 2015 were analyzed with text-mining and visualization methods. We found that the annual number of ERM publications is steadily increasing, and identified and described four distinct research clusters focusing on integration & operational effectiveness, innovation & value creation, inter-organizational relationships, and knowledge transfer & learning. The identification of research clusters and key works and authors in this multidisciplinary research field can assist future research in better positioning their studies and finding the key references across disciplinary silos.
|
|
| 8. |
- Kauppi, Anna, 1971-
(författare)
-
Chemical attenuation of bacterial virulence : small molecule inhibitors of type III secretion
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the large arsenal of antibiotics available on the market, treatment of bacterial infections becomes more challenging in view of the fact that microbes develop resistance against existing drugs. There is an obvious need for novel drugs acting on both old and new targets in bacteria. In this thesis we have employed a whole cell bacterial assay for screening and identification of type III secretion system (T3SS) inhibitors in Yersinia pseudotuberculosis. The T3SS is a common virulence mechanism utilized by several clinically relevant Gram-negative bacteria including Salmonella, Shigella, Pseudomonas aeruginosa, Chlamydiae and Escherichia coli. Several components in the T3SS have proved to be conserved and hence data generated with Y. pseudotuberculosis as model might also be valid for other bacterial species. We have screened a 9,400 commercial compound library for T3S inhibitors in Y. pseudotuberculosis using a yopE reporter gene assay. The initial ~ 30 hits were followed up in a growth inhibition assay resulting in 26 interesting compounds that were examined in more detail. Three of the most interesting compounds, salicylanilides, 2-hydroxybenzylidene-hydrazides and 2-arylsulfonamino-benzanilides, were selected for continued investigations. The inhibitor classes show different profiles regarding the effects on T3SS in Yersinia and their use as research tools and identification of the target proteins using a chemical biology approach will increase our understanding of bacterial virulence. The 2-hydroxybenzylidene-hydrazides have been extensively studied in vitro and show potential as selective T3S inhibitors in several Gram-negative pathogens besides Y. pseudotuberculosis. The data obtained suggest that this inhibitor class targets a conserved protein in the secretion apparatus. In cell-based ex vivo infection models T3SS was inhibited to the advantage of the infected eukaryotic cells. The salicylanilides and 2-arylsulfonamino-benzanilides have been further investigated by statistical molecular design (SMD) followed by synthesis and biological evaluation in the T3SS linked reporter gene assay. Multivariate QSAR models were established despite the challenges with data obtained from assays using viable bacteria. Our results indicate that this SMD QSAR strategy is powerful in development of virulence inhibitors targeting the T3SS.
|
|
| 9. |
- Kauppi, Anna M., et al.
(författare)
-
Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room
- 2016
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Kauppi, Anna, 1971-, et al.
(författare)
-
Targeting bacterial Virulence : Inhibitors of type III secretion in Yersinia
- 2003
-
Ingår i: Chemistry and Biology. - 1074-5521 .- 1879-1301. ; 10:3, s. 241-249
-
Tidskriftsartikel (refereegranskat)abstract
- Agents that target bacterial virulence without detrimental effect on bacterial growth are useful chemical probes for studies of virulence and potential candidates for drug development. Several gram-negative pathogens employ type III secretion to evade the innate immune response of the host. Screening of a chemical library with a luciferase reporter gene assay in viable Yersinia pseudotuberculosis furnished several compounds that inhibit the reporter gene signal expressed from the yopE promoter and effector protein secretion at concentrations with no or modest effect on bacterial growth. The selectivity patterns observed for inhibition of various reporter gene strains indicate that the compounds target the type III secretion machinery at different levels. Identification of this set of inhibitors illustrates the approach of utilizing cell-based assays to identify compounds that affect complex bacterial virulence systems.
|
|
| 13. |
- Kauppi, Laura, et al.
(författare)
-
Marine heatwaves of differing intensities lead to distinct patterns in seafloor functioning
- 2022
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 289:1986
-
Tidskriftsartikel (refereegranskat)abstract
- Marine heatwaves (MHWs) are increasing in frequency and intensity due to climate change. Several well-documented effects of heatwaves on community structure exist, but examples of their effect on functioning of species, communities or ecosystems remain scarce. We tested the effects of short-term, moderate and strong MHWs on macrofauna bioturbation and associated solute fluxes as examples of ecosystem functioning. We also measured macrofaunal excretion rates to assess effects of temperature on macrofauna metabolism. For this experiment, we used unmanipulated sediment cores with natural animal communities collected from a muddy location at 32 m depth in the northern Baltic Sea. Despite the mechanistic effect of bioturbation remaining unchanged between the treatments, there were significant differences in oxygen consumption, solute fluxes and excretion. Biogeochemical and biological processes were boosted by the moderate heatwave, whereas biogeochemical cycling seemed to decrease under a strong heatwave. A prolonged, moderate heatwave could possibly lead to resource depletion if primary production cannot meet the demands of benthic consumption. By contrast, decreased degradation activities under strong heatwaves could lead to a build-up of organic material and potentially hypoxia. The strong variability and the complexity of the response highlight the context dependency of these processes complicating future predictions.
|
|
| 14. |
- Müller, Daniel C., et al.
(författare)
-
Phospholipid Levels in Blood during Community-Acquired Pneumonia
- 2019
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:5
-
Tidskriftsartikel (refereegranskat)abstract
- Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.
|
|
| 15. |
- Nordfelth, R., et al.
(författare)
-
Small-molecule inhibitors specifically targeting type III secretion
- 2005
-
Ingår i: Infection and Immunity. - Washington : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 73:5, s. 3104-3114
-
Tidskriftsartikel (refereegranskat)abstract
- The type III secretion (TTS) system is used by several animal and plant pathogens to deliver effector proteins into the cytosol of the eukaryotic target cell as a strategy to evade the defense reactions elicited by the infected organism. The fact that these systems are highly homologous implies that novel antibacterial agents that chemically attenuate the pathogens via a specific interaction with the type III secretion mechanism can be identified. A number of small organic molecules having this potential have recently been identified (A. M. Kauppi, R. Nordfelth, H. Uvell, H. Wolf-Watz, and M. Elofsson, Chem. Biol. 10:241-249, 2003). Using different reporter gene constructs, we showed that compounds that belong to a class of acylated hydrazones of different salicylaldehydes target the TTS system of Yersinia pseudotuberculosis. One of these compounds, compound 1, was studied in detail and was found to specifically block Yop effector secretion under in vitro conditions by targeting the TTS system. In this respect the drug mimics the well-known effect of calcium on Yop secretion. In addition, compound I inhibits Yop effector translocation after infection of HeLa cells without affecting the eukaryotic cells or the bacteria. A HeLa cell model that mimics in vivo conditions showed that compound 1 chemically attenuates the pathogen to the advantage of the eukaryotic cell. Thus, our results show proof of concept, i.e., that small compounds targeting the TTS system can be identified, and they point to the possible use of TTS inhibitors as a novel class of antibacterial agents.
|
|
| 16. |
|
|
| 17. |
- Tanskanen, Kari, et al.
(författare)
-
Towards evidence-based management of external resources: developing design propositions and future research avenues through research synthesis
- 2017
-
Ingår i: Research Policy. - : Elsevier BV. - 0048-7333. ; 46:6, s. 1087-1105
-
Tidskriftsartikel (refereegranskat)abstract
- The general question of how best to access and leverage resources that reside outside the boundaries of the focal firm has become increasingly important for companies during the last decennia, and scholars across management disciplines have responded with increasing research efforts. However, managers still seldom base their decisions on scientific evidence. Research on managing external resources is carried out in disciplinary silos and it is extremely difficult for managers to make sense of the vast amount of scientific studies. The success story of medicine as the first domain to widely adopt evidence-based practices has been an exemplar for other disciplines such as management to address the prevailing research-practice gap. Through a systematic review and synthesis of 601 articles in six academic journals representing three management disciplines we develop design propositions for supporting evidence-based management of external resources in firms. Our analysis reveals external resource management (ERM) research to be concentrated on six distinct, yet interrelated, themes. We adopt the CIMO-logic (Context, Intervention, Mechanism, Outcomes) for developing the set of design propositions within each of the research themes. A key scientific contribution is our identification of future research opportunities and directions to advance science in the field of ERM.
|
|
| 18. |
- Wang, Xiaoyang, et al.
(författare)
-
Efficient Solution-Phase Parallel Synthesis of 4-Substituted N-Protected Piperidines
- 2003
-
Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 23, s. 4586-92
-
Tidskriftsartikel (refereegranskat)abstract
- Practical conditions for the synthesis of 4-substituted N-protected piperidines through CuCN·2LiBr-catalyzed organozinc additions to 1-acylpyridinium salts and subsequent hydrogen-transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4-substituted N-protected piperidines in excellent overall yields without the isolation of intermediate dihydropyridines. In those cases in which the organozinc addition results in mixtures of 2- and 4-substituted dihydropyridines, the 2-substituted isomers are efficiently scavenged with maleic anhydride and subsequently removed by a mild extractive workup with NaHCO3 (sat.). The N-acyl group can conveniently be exchanged from N-phenoxycarbonyl to N-tBoc, thus allowing orthogonal deprotection strategies.
|
|
